Literature detail

ACE2 receptor usage reveals variation in susceptibility to SARS-CoV and SARS-CoV-2 infection among bat species.

Huan Yan¹ Hengwu Jiao² Qianyun Liu¹ Zhen Zhang¹ Qing Xiong¹ Bing-Jun Wang² Xin Wang¹ Ming Guo¹ Lin-Fa Wang³ Ke Lan^4,5 Yu Chen⁶ Huabin Zhao^7,8

Affiliations 8 institutions

State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
Department of Ecology, Tibetan Centre for Ecology and Conservation at WHU-TU, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.
Duke-NUS Medical School, Singapore, Singapore.
State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China. [email protected].
Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China. [email protected].
State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China. [email protected].
State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China. [email protected].
Department of Ecology, Tibetan Centre for Ecology and Conservation at WHU-TU, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China. [email protected].

PMID 33649547 2021 Nat Ecol Evol eng ppublish

PubMed DOI Browse context

Article

Publication summary

Bats are the suggested natural hosts for severe acute respiratory syndrome coronavirus (SARS-CoV) and the causal agent of the coronavirus disease 2019 (COVID-19) pandemic, SARS-CoV-2. The interaction of viral spike proteins with their host receptor angiotensin-converting enzyme 2 (ACE2) is a critical determinant of potential hosts and cross-species transmission. Here we use virus-host receptor binding and infection assays to examine 46 ACE2 orthologues from phylogenetically diverse bat species, including those in close and distant contact with humans. We found that 24, 21 and 16 of them failed to support infection by SARS-CoV, SARS-CoV-2 or both viruses, respectively. Furthermore, we confirmed that infection assays in human cells were consistent with those in two bat cell lines. Additionally, we used genetic and functional analyses to identify critical residues in bat ACE2 receptors associated with viral entry restrictions. Our results suggest that many bat species may not be the potential hosts of one or both viruses and that no correlation was identified between proximity to humans and probability of being natural hosts of SARS-CoV or SARS-CoV-2. This study demonstrates dramatic variation in susceptibility to SARS-CoV and SARS-CoV-2 infection among bat species and adds knowledge towards a better understanding of coronavirus-bat interaction.

Chiroptera COVID-19 Angiotensin-Converting Enzyme 2 Animals Humans Peptidyl-Dipeptidase A Receptors, Virus SARS-CoV-2 Spike Glycoprotein, Coronavirus

Structured evidence records

Evidence records

6 total

Host Range Experiment 2 records

Host Range Experiment Extraction confidence 0.95

Key finding

Experimental infection assays using 46 bat ACE2 orthologues revealed that susceptibility to SARS-CoV and SARS-CoV-2 infection varies among bat species.

Virus

Host

Location

Supporting text

Here we use virus-host receptor binding and infection assays to examine 46 ACE2 orthologues from phylogenetically diverse bat species... We found that 24, 21 and 16 of them failed to support infection by SARS-CoV, SARS-CoV-2 or both viruses, respectively.

Method: virus-host receptor binding assay; infection assay
Experimental system: in vitro cell culture

Host Range Experiment Extraction confidence 0.95

Key finding

Experimental infection assays indicated that many bat ACE2 orthologues do not support SARS-CoV-2 infection, demonstrating heterogeneous susceptibility among bat species.

Virus

Host

Location

Supporting text

Method: virus-host receptor binding assay; infection assay
Experimental system: in vitro cell culture

Molecular Adaptation 2 records

Molecular Adaptation Extraction confidence 0.90

Key finding

Specific amino acid residues in bat ACE2 receptors were linked to differential SARS-CoV and SARS-CoV-2 entry, indicating molecular determinants of host susceptibility.

Virus

Host

Location

Supporting text

We used genetic and functional analyses to identify critical residues in bat ACE2 receptors associated with viral entry restrictions.

Genes or proteins: spike; ACE2
Receptors: ACE2
Mechanism types: receptor_binding; cell_entry; host_factor_interaction

Molecular Adaptation Extraction confidence 0.90

Key finding

Differences in bat ACE2 receptor residues affected SARS-CoV-2 spike-mediated entry, reflecting molecular adaptation influencing host susceptibility.

Virus

Host

Location

Supporting text

We used genetic and functional analyses to identify critical residues in bat ACE2 receptors associated with viral entry restrictions.

Genes or proteins: spike; ACE2
Receptors: ACE2
Mechanism types: receptor_binding; cell_entry; host_factor_interaction

Receptor Usage 2 records

Receptor Usage Extraction confidence 1.00

Key finding

Bat ACE2 orthologues showed variable compatibility with SARS-CoV and SARS-CoV-2 spike proteins, as some failed to support viral entry in infection assays.

Virus

Host

Location

Supporting text

Here we use virus-host receptor binding and infection assays to examine 46 ACE2 orthologues from phylogenetically diverse bat species, including those in close and distant contact with humans. We found that 24, 21 and 16 of them failed to support infection by SARS-CoV, SARS-CoV-2 or both viruses, respectively.

Method: receptor binding assay; infection assay
Receptors: ACE2

Receptor Usage Extraction confidence 1.00

Key finding

Bat ACE2 orthologues vary in their ability to support SARS-CoV-2 binding and entry, with some failing to permit infection.

Virus

Host

Location

Supporting text

Method: receptor binding assay; infection assay
Receptors: ACE2

Citation context

References

40 references

Reference network

Force-directed citation graph. OmniVira-indexed references are prioritized and recursively expanded up to three steps.

260 nodes · 511 links · capped

Drag nodes to explore citation neighborhoods


PMID 32015507	A pneumonia outbreak associated with a new coronavirus of probable bat origin	Zhou	2020
PMID 16195424	Bats are natural reservoirs of SARS-like coronaviruses	Li	2005
PMID 29190287	Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus	Hu	2017
PMID 32217719	COVID-19 drives new threat to bats in China	Zhao	2020
-	Handbook of the Mammals of the World	Wilson	2009
PMID 14647384	Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus	Li	2003
-	Functional and genetic analysis of viral receptor ACE2 orthologs reveals broad potential host range of SARS-CoV-2. Preprint at	Liu	2020
PMID 33335073 In OmniVira	Cross-species recognition of SARS-CoV-2 to bat ACE2.	Liu	2021
PMID 32826334 In OmniVira	Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates.	Damas	2020
PMID 15731278	Exogenous ACE2 expression allows refractory cell lines to support severe acute respiratory syndrome coronavirus replication	Mossel	2005
PMID 14670965	K., Li, W., Moore, M	Wong	2004
PMID 32203189 In OmniVira	Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine.	Tai	2020
PMID 32075877 In OmniVira	Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.	Wrapp	2020
PMID 32225175 In OmniVira	Structural basis of receptor recognition by SARS-CoV-2.	Shang	2020
PMID 32207377	Establishment and validation of a pseudovirus neutralization assay for SARS-CoV-2	Nie	2020
PMID 16169905	Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats	Lau	2005
PMID 32697968	Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus	Korber	2020
-	The D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity and decreases neutralization sensitivity to individual convalescent sera. Preprint at bioRxiv	Hu	2020
PMID 33271067	Cryo-EM structures of SARS-CoV-2 spike without and with ACE2 reveal a pH-dependent switch to mediate endosomal positioning of receptor-binding domains	Zhou	2020
PMID 32758356	How to measure and evaluate binding affinities. eLife 9, e57264 (2020)	Jarmoskaite	2020
PMID 32699095	Evolutionary arms race between virus and host drives genetic diversity in bat severe acute respiratory syndrome-related related coronavirus spike genes	Guo	2020
-	Bats and coronaviruses	Banerjee	2019
PMID 32881980	Possibility for reverse zoonotic transmission of SARS-CoV-2 to free-ranging wildlife: a case study of bats	Olival	2020
PMID 32269068	Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2	Shi	2020
PMID 30937915	F., Kingston, T. & Flanders, J. A review of the major threats and challenges to global bat conservation. Ann. N. Y	Frick	2020
PMID 15034147	MUSCLE: multiple sequence alignment with high accuracy and high throughput	Edgar	2004
PMID 24105918	PAMLX: a graphical user interface for PAML	Xu	2013
PMID 15681385	A molecular phylogeny for bats illuminates biogeography and the fossil record	Teeling	2005
-	C., Simmons, N. B. & Giannini, N. P	Almeida	2020
PMID 26865275	Bats (Chiroptera: Noctilionoidea) challenge a recent origin of extant neotropical diversity	Rojas	2016
PMID 16033974	Vesicular stomatitis virus pseudotyped with severe acute respiratory syndrome coronavirus spike protein	Fukushi	2005
PMID 19264610	Comparison of vesicular stomatitis virus pseudotyped with the S proteins from a porcine and a human coronavirus	Schwegmann-Weßels	2009
PMID 20709108	Generation of VSV pseudotypes using recombinant ΔG-VSV for studies on virus entry, identification of entry inhibitors, and immune responses to vaccines	Whitt	2010
PMID 25549265	The I-TASSER Suite: protein structure and function prediction	Yang	2015
PMID 32275855 In OmniVira	Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.	Wang	2020
PMID 12875852	Protein–protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations	Gray	2003
PMID 23139141	A comparison of successful and failed protein interface designs highlights the challenges of designing buried hydrogen bonds	Stranges	2013
PMID 27198219	The RING 2.0 web server for high quality residue interaction networks	Piovesan	2016
PMID 21919503	LigPlot+: multiple ligand–protein interaction diagrams for drug discovery	Laskowski	2011
PMID 27926832	S., Filipek, S. & Vogel, H. PyMOL and Inkscape bridge the data and the data visualization. Structure 24, 2041–2042 (2016)	Yuan	2016

Evidence overview

Evidence 6

Types 3

Virus 2

Host 1

Evidence types

Host Range Experiment 2 Molecular Adaptation 2 Receptor Usage 2

Linked entities

Viruses

Hosts

Locations

Publication metadata

Journal: Nature ecology & evolution
Volume / Issue / Pages: 5 / 5 / 600-608
ISSN: 2397-334X
Journal country: England
DOI: 10.1038/s41559-021-01407-1